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Specific Virus-Host Genome Interactions Revealed by Tethered Chromosome Conformation Capture

Haochen Li, Reza Kalhor, Bing Li, Trent Su, Arnold J. Berk, Siavash K. Kurdistani, Frank Alber, Lin Chen
doi: https://doi.org/10.1101/142604
Haochen Li
aMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
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Reza Kalhor
aMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
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Bing Li
bDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Trent Su
bDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
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Arnold J. Berk
cDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
dMolecular Biology Institute, University of California, Los Angeles, CA 90095, USA
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Siavash K. Kurdistani
bDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
dMolecular Biology Institute, University of California, Los Angeles, CA 90095, USA
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Frank Alber
aMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
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  • For correspondence: alber@usc.edu linchen@usc.edu
Lin Chen
aMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
eDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089, USA
fNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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  • For correspondence: alber@usc.edu linchen@usc.edu
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Abstract

Viruses have evolved a variety of mechanisms to interact with host cells for their adaptive benefits, including subverting host immune responses and hijacking host DNA replication/transcription machineries [1–3]. Although interactions between viral and host proteins have been studied extensively, little is known about how the vial genome may interact with the host genome and how such interactions could affect the activities of both the virus and the host cell. Since the three-dimensional organization of a genome can have significant impact on genomic activities such as transcription and replication, we hypothesize that such structure-based regulation of genomic functions also applies to viral genomes depending on their association with host genomic regions and their spatial locations inside the nucleus. Here, we used Tethered Chromosome Conformation Capture (TCC) to investigate viral-host genome interactions between the adenovirus and human lung fibroblast cells. We found viral-host genome interactions were enriched in certain active chromatin regions and chromatin domains marked by H3K27me3. The contacts by viral DNA seems to impact the structure and function of the host genome, leading to remodeling of the fibroblast epigenome. Our study represents the first comprehensive analysis of viral-host interactions at the genome structure level, revealing unexpectedly specific virus-host genome interactions. The non-random nature of such interactions indicates a deliberate but poorly understood mechanism for targeting of host DNA by foreign genomes.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 26, 2017.
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Specific Virus-Host Genome Interactions Revealed by Tethered Chromosome Conformation Capture
Haochen Li, Reza Kalhor, Bing Li, Trent Su, Arnold J. Berk, Siavash K. Kurdistani, Frank Alber, Lin Chen
bioRxiv 142604; doi: https://doi.org/10.1101/142604
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Specific Virus-Host Genome Interactions Revealed by Tethered Chromosome Conformation Capture
Haochen Li, Reza Kalhor, Bing Li, Trent Su, Arnold J. Berk, Siavash K. Kurdistani, Frank Alber, Lin Chen
bioRxiv 142604; doi: https://doi.org/10.1101/142604

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